当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Antitumor agents 288: design, synthesis, SAR, and biological studies of novel heteroatom-incorporated antofine and cryptopleurine analogues as potent and selective antitumor agents.

Antitumor agents 288: design, synthesis, SAR, and biological studies of novel heteroatom-incorporated antofine and cryptopleurine analogues as potent and selective antitumor agents.

Abstract：

:Novel heteroatom-incorporated antofine and cryptopleurine analogues were designed, synthesized, and tested against a panel of five cancer cell lines. Two new S-13-oxo analogues (11 and 16) exhibited potent cell growth inhibition in vitro (GI(50): 9 nM and 20 nM). Interestingly, both compounds displayed improved selectivity among different cancer cell lines, in contrast to the natural products antofine and cryptopleurine. Mechanism of action (MOA) studies suggested that R-antofine promotes dysregulation of DNA replication during early S phase, while no similar effects were observed for 11 and 15 on corresponding replication initiation complexes. Compound 11 also showed greatly reduced cytotoxicity against normal cells and moderate antitumor activity against HT-29 human colorectal adenocarcinoma xenograft in mice without overt toxicity.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Yang X,Shi Q,Yang SC,Chen CY,Yu SL,Bastow KF,Morris-Natschke SL,Wu PC,Lai CY,Wu TS,Pan SL,Teng CM,Lin JC,Yang PC,Lee KH

doi

10.1021/jm200330s

subject

Has Abstract

pub_date

2011-07-28 00:00:00

pages

5097-107

issue

14

eissn

0022-2623

issn

1520-4804

journal_volume

54

pub_type

杂志文章

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